This application relates to a probe for detecting a substance in the body useful as an instrument for detecting a substance in the body in gingival crevicular fluid. More specifically, the present application is concerned with a probe for detecting a substance in the body for permitting optical detection of a substance in the body in gingival crevicular fluid and also with a system for detecting a substance in the body making use of the probe for detecting a substance in the body.
For the detection of a substance in the body, it is generally a common practice to collect blood and then to optically or electrically analyze the substance in the body in the blood. However, the collection of blood is an invasive method, needs medical qualifications or the like for a phlebotomist, and moreover, is costly. Further, purification of blood is needed in actual detection or measurement, thereby involving a problem in that labor and time are needed to obtain the detection or measurement results. In addition, continuous measurement requires an increased number of sampling, so that a substantial burden is imposed on a subject under test. There is, accordingly, another problem in that no real-time measurement is feasible.
Therefore, a variety of methods have been being developed in recent years to reduce the invasiveness to the body. Taking as an example the measurement of blood sugar level, noninvasive and low-invasive measuring methods will be described hereinafter.
The noninvasive measuring methods include a method that is applied to the dermis, arm, finger tip or the like and determines the glucose level in blood by measuring a scattering transmission spectrum with infrared light, a method that is applied to the labial mucosa and determines the glucose level in blood by measuring a scattering spectrum with infrared light, a method that is applied to the finger tip and determines the glucose level in blood by measuring a Raman scattering spectrum, and a method that is applied to the skin and determines the glucose level in blood by performing photoacoustic measurement.
These noninvasive measuring methods are, however, accompanied by a problem in that they are inferior in accuracy to the measuring method that relies upon the collection of blood although they can measure the blood glucose level in real time.
On the other hand, the low-invasive measuring methods include a method that measures the glucose level in body fluid (intercellular fluid) by collecting the body fluid from the arm on the same principle of iontophoresis, a method that measures the glucose level in body fluid by collecting the body fluid from the skin under ultrasonic waves, a method that measures the glucose level in body fluid by collecting the body fluid from the arm with a patch or cannula, a method that measures the glucose level in lacrimal fluid by collecting the lacrimal fluid from the eye and conducting fluorescent measurement, a method that measures the glucose level in lacrimal fluid by collecting the lacrimal fluid from the eye and conducting holographic diffraction, a method that measures the glucose level in saliva by collecting the saliva from the mouth, and a method that measures the glucose level in urine by collecting the urine.
These low-invasive measuring methods are, however, accompanied by problems such that they cannot perform real-time measurement because the glucose level in body fluid is delayed by 30 minutes or so compared with the corresponding glucose level in blood, that they are difficult to perform accurate measurement of the concentration of glucose because the concentration of glucose in body fluid, lacrimal fluid, saliva or urine is as low as 1/10 or less of the concentration of glucose in blood, and that they can hardly perform accurate measurement of a glucose level because stable sampling is difficult for the collection of saliva from the mouth.
In the meantime, a method has been under development as a noninvasive measuring method to detect a substance in the body in gingival crevicular fluid. It is known that the glucose level, for example, in gingival crevicular fluid changes with time in substantial conformity with the glucose level in blood. It is, therefore, possible to perform the diagnosis, treatment and control of diabetes by measuring the glucose level in gingival crevicular fluid.
Concerning the activity of aspartic acid aminotransferase (AST) and that of alanine aminotransferase (ALT) as parameters of liver function, on the other hand, their values in gingival crevicular fluid are known to correlate to the corresponding values in blood. It is, therefore, possible to determine the degree of a loss of liver function by measuring the AST activity and ALT activity in gingival crevicular fluid.
As a technology for measuring a substance in the body in gingival crevicular fluid as described above, Japanese Patent Laid-open No. 2001-201437 discloses a technology relating to a capillary device that can draw up gingival crevicular fluid under capillary action based on a concept to noninvasively estimate biological information such as a glucose level from the concentration of a chemical substance contained in gingival crevicular fluid.
Further, Japanese Patent Laid-open No. 2005-283366 discloses a collection instrument which as viewed in transverse section, is formed of a shell portion and plural rib portions extending in centripetal directions from the shell portion. Between these rib portions, a plurality of capillary passages are formed through the collection instrument from its one end to its opposite end to draw up fluid. The collection instrument can, therefore, collect body fluid in a predetermined constant microamount as small as several microliters or less from a site of collection in a pinpoint manner.
These technologies, however, need cumbersome handling of a sample, are time-consuming and laborious and require skill, because they rely upon a method that collects body fluid such as gingival crevicular fluid with the above-described capillary device or collection instrument and then measures the level of a substance in the body in the collected body fluid. In addition, it is necessary for continuous measurement to frequently perform sampling. As a matter of fact, the above-described technologies cannot measure the level of a substance in the body in real time.